Interactions between ExeFen-DM and Zonisamide
1 drug interaction and 22 additional warnings found for the following 2 drugs:
- ExeFen-DM (dextromethorphan/guaifenesin)
- zonisamide
Drug interactions
Moderate drug interactions
Moderate:
dextromethorphan zonisamide
Applies to: ExeFen-DM (dextromethorphan / guaifenesin) and zonisamide
Monitor
Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.
Management
During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
References (36)
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- Sotaniemi EA, Anttila M, Rautio A, et al. (1981) "Propranolol and sotalol metabolism after a drinking party." Clin Pharmacol Ther, 29, p. 705-10
- Grabowski BS, Cady WJ, Young WW, Emery JF (1980) "Effects of acute alcohol administration on propranolol absorption." Int J Clin Pharmacol Ther Toxicol, 18, p. 317-9
- Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF (1988) "The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam." Clin Pharmacol Ther, 43, p. 412-9
- MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol, 11, p. 345-9
- Divoll M, Greenblatt DJ, Lacasse Y, Shader RI (1981) "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl), 73, p. 381-3
- Naylor GJ, McHarg A (1977) "Profound hypothermia on combined lithium carbonate and diazepam treatment." Br Med J, 2, p. 22
- Stovner J, Endresen R (1965) "Intravenous anaesthesia with diazepam." Acta Anaesthesiol Scand, 24, p. 223-7
- Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF (1984) "Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation." J Pharm Pharmacol, 36, p. 244-7
- Feldman SA, Crawley BE (1970) "Interaction of diazepam with the muscle-relaxant drugs." Br Med J, 1, p. 336-8
- Ochs HR, Greenblatt DJ, Verburg-Ochs B (1984) "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther, 36, p. 451-5
- Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF (1988) "Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic." Psychopharmacology (Berl), 96, p. 63-6
- Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I (1989) "Midazolam-morphine sedative interaction in patients." Anesth Analg, 68, p. 282-5
- "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc
- Greiff JMC, Rowbotham D (1994) "Pharmacokinetic drug interactions with gastrointestinal motility modifying agents." Clin Pharmacokinet, 27, p. 447-61
- Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G (1989) "The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine." Acta Psychiatr Scand, 80 Suppl, p. 95-8
- Markowitz JS, Wells BG, Carson WH (1995) "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother, 29, p. 603-9
- (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
- (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories
- (2001) "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc)
- (2001) "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals
- (2001) "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company
- (2001) "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals
- Miller LG (1998) "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med, 158, p. 2200-11
- (2001) "Product Information. Precedex (dexmedetomidine)." Abbott Pharmaceutical
- (2001) "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals
- Ferslew KE, Hagardorn AN, McCormick WF (1990) "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci, 35, p. 477-82
- Plushner SL (2000) "Valerian: valeriana officinalis." Am J Health Syst Pharm, 57, p. 328-35
- (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc
- (2002) "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2014) "Product Information. Belsomra (suvorexant)." Merck & Co., Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
dextromethorphan Food/Lifestyle
Applies to: ExeFen-DM (dextromethorphan / guaifenesin)
Generally avoid
Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.
Management
Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
References (4)
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Moderate:
zonisamide Food/Lifestyle
Applies to: zonisamide
Generally avoid
Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.
Management
Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
References (4)
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Disease interactions
20 potential interactions Applies to: 17 conditions, including Depression, Allergies, Asthma, COPD, and Seizures.
Acidosis
Moderate:
zonisamide
Zonisamide has a moderate potential interaction with Acidosis.
Reduced plasma bicarbonate levels and, in some instances, elevated plasma chloride levels may result in metabolic acidosis during long-term therapy with carbonic anhydrase inhibitors. Therapy with carbonic anhydrase inhibitors should be administered cautiously in patients with metabolic or hyperchloremic acidosis or with conditions that predispose to acidosis (renal disease, severe respiratory disorders, diarrhea). The measurement of baseline and periodic serum bicarbonate is recommended. If metabolic acidosis develops (it may be corrected by administration of sodium bicarbonate), and persists, a dose reduction or treatment discontinuation should be considered.
Allergies
Major:
zonisamide
Zonisamide has a major potential interaction with Allergies.
The use of sulfonamides is associated with large increases in the risk of Stevens-Johnson syndrome, toxic epidermal necrolysis and other serious dermatologic reactions, although these phenomena are rare as a whole. Hepatitis, pneumonitis, and interstitial nephritis have also occurred in association with sulfonamide hypersensitivity. Therapy with sulfonamides should be administered cautiously in patients with severe allergies, bronchial asthma or AIDS, since these patients may be at increased risk for potentially severe hypersensitivity reactions. Patients should be instructed to promptly report signs and symptoms that may precede the onset of cutaneous manifestations of the Stevens-Johnson syndrome, such as high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Sulfonamide therapy should be stopped at once if a rash develops.
Asthma
Major:
zonisamide
Zonisamide has a major potential interaction with Asthma.
The use of sulfonamides is associated with large increases in the risk of Stevens-Johnson syndrome, toxic epidermal necrolysis and other serious dermatologic reactions, although these phenomena are rare as a whole. Hepatitis, pneumonitis, and interstitial nephritis have also occurred in association with sulfonamide hypersensitivity. Therapy with sulfonamides should be administered cautiously in patients with severe allergies, bronchial asthma or AIDS, since these patients may be at increased risk for potentially severe hypersensitivity reactions. Patients should be instructed to promptly report signs and symptoms that may precede the onset of cutaneous manifestations of the Stevens-Johnson syndrome, such as high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Sulfonamide therapy should be stopped at once if a rash develops.
Bone Marrow Depression/Low Blood Counts
Major:
zonisamide
Zonisamide has a major potential interaction with Bone Marrow Depression/Low Blood Counts.
The use of carbonic anhydrase inhibitors may rarely cause bone marrow suppression and blood dyscrasias at recommended dosages. Aplastic anemia, thrombocytopenia or thrombocytopenia purpura, leukopenia, agranulocytosis, and hemolytic anemia have been reported. Extreme caution should be exercised if carbonic anhydrase inhibitors are administered to patients with these preexisting conditions. A baseline CBC and platelet count is recommended, as well as monitoring at regular intervals during therapy.
Major:
zonisamide
Zonisamide has a major potential interaction with Bone Marrow Depression/Low Blood Counts.
The use of sulfonamides has been associated with hematologic toxicity, including methemoglobinemia, sulfhemoglobinemia, leukopenia, granulocytopenia, eosinophilia, hemolytic anemia, aplastic anemia, purpura, clotting disorder, thrombocytopenia, hypofibrinogenemia, and hypoprothrombinemia. Acute dose-related hemolytic anemia may occur during the first week of therapy due to sensitization, while chronic hemolytic anemia may occur with prolonged use. Patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency should be observed closely for signs of hemolytic anemia. Therapy with sulfonamides should be administered cautiously in patients with preexisting blood dyscrasias or bone marrow suppression. Complete blood counts should be obtained regularly, especially during prolonged therapy (>2 weeks), and patients should be instructed to immediately report any signs or symptoms suggestive of blood dyscrasia such as fever, sore throat, local infection, bleeding, pallor, dizziness, or jaundice.
COPD
Moderate:
zonisamide
Zonisamide has a moderate potential interaction with COPD.
Reduced plasma bicarbonate levels and, in some instances, elevated plasma chloride levels may result in metabolic acidosis during long-term therapy with carbonic anhydrase inhibitors. Therapy with carbonic anhydrase inhibitors should be administered cautiously in patients with metabolic or hyperchloremic acidosis or with conditions that predispose to acidosis (renal disease, severe respiratory disorders, diarrhea). The measurement of baseline and periodic serum bicarbonate is recommended. If metabolic acidosis develops (it may be corrected by administration of sodium bicarbonate), and persists, a dose reduction or treatment discontinuation should be considered.
Dehydration
Moderate:
zonisamide
Zonisamide has a moderate potential interaction with Dehydration.
The use of zonisamide may infrequently be associated with the development of nephrolithiasis. The reported incidence for clinically possible or confirmed kidney stones was 4.0% (40 of 991 patients) during premarketing use, representing a rate of 34 per 1000 patient-years of exposure (40 patients with 1168 years of exposure). Therapy with zonisamide should be administered cautiously with adequate hydration in patients with a history of nephrolithiasis. Patients who are dehydrated may be at increased risk for the development of nephrolithiasis and should be encouraged to consume additional amounts of liquid during zonisamide therapy.
Depression
Major:
zonisamide
Zonisamide has a major potential interaction with Depression.
Antiepileptic drugs including zonisamide can increase depression and suicidal thoughts or behaviors in patients receiving these drugs for any indication. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts and unusual changes in mood or behavior. Caregivers and family should be alert for the emergence or worsening of symptoms. Behaviors of concern should be reported immediately to the healthcare providers.
Moderate:
zonisamide
Zonisamide has a moderate potential interaction with Depression.
Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.
Diarrhea
Moderate:
zonisamide
Zonisamide has a moderate potential interaction with Diarrhea.
Reduced plasma bicarbonate levels and, in some instances, elevated plasma chloride levels may result in metabolic acidosis during long-term therapy with carbonic anhydrase inhibitors. Therapy with carbonic anhydrase inhibitors should be administered cautiously in patients with metabolic or hyperchloremic acidosis or with conditions that predispose to acidosis (renal disease, severe respiratory disorders, diarrhea). The measurement of baseline and periodic serum bicarbonate is recommended. If metabolic acidosis develops (it may be corrected by administration of sodium bicarbonate), and persists, a dose reduction or treatment discontinuation should be considered.
Fever
Major:
zonisamide
Zonisamide has a major potential interaction with Fever.
Oligohidrosis (decreased sweating) and hyperthermia have been reported in association with the use of some carbonic anhydrase inhibitor anticonvulsants such as topiramate and zonisamide. Most of the reports have been in children. Caution and close monitoring of body temperature is advised when prescribing these drugs, especially in patients with a fever, in hot weather, or if combined with other drugs that predispose to heat related disorders. Zonisamide is not approved for use in pediatric patients in the U.S.
History, Nephrolithiasis
Moderate:
zonisamide
Zonisamide has a moderate potential interaction with History, Nephrolithiasis.
The use of zonisamide may infrequently be associated with the development of nephrolithiasis. The reported incidence for clinically possible or confirmed kidney stones was 4.0% (40 of 991 patients) during premarketing use, representing a rate of 34 per 1000 patient-years of exposure (40 patients with 1168 years of exposure). Therapy with zonisamide should be administered cautiously with adequate hydration in patients with a history of nephrolithiasis. Patients who are dehydrated may be at increased risk for the development of nephrolithiasis and should be encouraged to consume additional amounts of liquid during zonisamide therapy.
History of Blood Dyscrasias
Major:
zonisamide
Zonisamide has a major potential interaction with History of Blood Dyscrasias.
The use of carbonic anhydrase inhibitors may rarely cause bone marrow suppression and blood dyscrasias at recommended dosages. Aplastic anemia, thrombocytopenia or thrombocytopenia purpura, leukopenia, agranulocytosis, and hemolytic anemia have been reported. Extreme caution should be exercised if carbonic anhydrase inhibitors are administered to patients with these preexisting conditions. A baseline CBC and platelet count is recommended, as well as monitoring at regular intervals during therapy.
HIV-1 Infection
Major:
zonisamide
Zonisamide has a major potential interaction with HIV-1 Infection.
The use of sulfonamides is associated with large increases in the risk of Stevens-Johnson syndrome, toxic epidermal necrolysis and other serious dermatologic reactions, although these phenomena are rare as a whole. Hepatitis, pneumonitis, and interstitial nephritis have also occurred in association with sulfonamide hypersensitivity. Therapy with sulfonamides should be administered cautiously in patients with severe allergies, bronchial asthma or AIDS, since these patients may be at increased risk for potentially severe hypersensitivity reactions. Patients should be instructed to promptly report signs and symptoms that may precede the onset of cutaneous manifestations of the Stevens-Johnson syndrome, such as high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Sulfonamide therapy should be stopped at once if a rash develops.
Liver Disease
Major:
zonisamide
Zonisamide has a major potential interaction with Liver Disease.
The use of carbonic anhydrase inhibitors is contraindicated in patients with marked liver disease or cirrhosis. Carbonic anhydrase inhibitors increase the risk of developing hepatic encephalopathy in these patients. Extreme caution should be exercised if carbonic anhydrase inhibitors are administered in patients with mild to moderate liver disease as the clearance of the drug can be decreased. A dose reduction might be needed and monitoring of the liver function is recommended.
Nephrolithiasis
Moderate:
zonisamide
Zonisamide has a moderate potential interaction with Nephrolithiasis.
The use of zonisamide may infrequently be associated with the development of nephrolithiasis. The reported incidence for clinically possible or confirmed kidney stones was 4.0% (40 of 991 patients) during premarketing use, representing a rate of 34 per 1000 patient-years of exposure (40 patients with 1168 years of exposure). Therapy with zonisamide should be administered cautiously with adequate hydration in patients with a history of nephrolithiasis. Patients who are dehydrated may be at increased risk for the development of nephrolithiasis and should be encouraged to consume additional amounts of liquid during zonisamide therapy.
Psychosis
Moderate:
zonisamide
Zonisamide has a moderate potential interaction with Psychosis.
Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.
Renal Dysfunction
Moderate:
zonisamide
Zonisamide has a moderate potential interaction with Renal Dysfunction.
Reduced plasma bicarbonate levels and, in some instances, elevated plasma chloride levels may result in metabolic acidosis during long-term therapy with carbonic anhydrase inhibitors. Therapy with carbonic anhydrase inhibitors should be administered cautiously in patients with metabolic or hyperchloremic acidosis or with conditions that predispose to acidosis (renal disease, severe respiratory disorders, diarrhea). The measurement of baseline and periodic serum bicarbonate is recommended. If metabolic acidosis develops (it may be corrected by administration of sodium bicarbonate), and persists, a dose reduction or treatment discontinuation should be considered.
Moderate:
zonisamide
Zonisamide has a moderate potential interaction with Renal Dysfunction.
The major route of elimination of carbonic anhydrase inhibitors is through the kidney. These drugs should be administered cautiously in patients with reduced renal function and a dose adjustment might be required depending on the level of impairment.
Seizures
Moderate:
zonisamide
Zonisamide has a moderate potential interaction with Seizures.
The abrupt withdrawal of zonisamide capsules in patients with epilepsy may precipitate the increase of seizure frequency or status epilepticus. Caution is advised when using this drug in patients with seizures. Dose reduction or discontinuation should be done gradually.
More resources
ExeFen-DM
A total of 375 drugs are known to interact with ExeFen-DM.
- Exefen-dm is in the drug class upper respiratory combinations.
- Exefen-dm is used to treat the following conditions:
zonisamide
A total of 426 drugs are known to interact with zonisamide.
- Zonisamide is in the drug class carbonic anhydrase inhibitor anticonvulsants.
-
Zonisamide is used to treat the following conditions:
- Benign Essential Tremor (off-label)
- Epilepsy
- Migraine Prevention (off-label)
- Parkinsonian Tremor (off-label)
- Seizures
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.